Glucagon
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Glucagon: Exploring a Predicted New Indication in Irritable Bowel Syndrome
One-Sentence Summary
No original indication or marketing history for Glucagon is recorded in this evidence pack for the UK market. The TxGNN model predicts potential effectiveness for Irritable Bowel Syndrome (IBS), supported by 11 clinical trials and 20 publications, though the great majority of this evidence concerns glucagon-like peptide-1 (GLP-1) receptor agonists rather than glucagon itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available — no UK marketing authorisation on record for this drug |
| Predicted New Indication | Irritable Bowel Syndrome |
| TxGNN Prediction Score | 99.24% |
| Evidence Level | L4 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data for Glucagon is currently unavailable in this evidence pack, and no original indication is recorded. This makes a direct pharmacological rationale difficult to construct from the data provided.
An important caveat needs to be raised here for clinical review. The clinical trial and literature evidence retrieved under “Glucagon” overwhelmingly concerns glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. ROSE-010, exenatide/exendin-4, liraglutide) rather than glucagon itself. Glucagon and GLP-1 are both derived from the same precursor gene, proglucagon, but they act on distinct receptors and have largely opposing physiological effects — glucagon raises blood glucose and is used to treat severe hypoglycaemia, whereas GLP-1 receptor agonists lower blood glucose, slow gastric emptying, and are the agents actually studied for gut-motility effects in IBS. It is plausible that the TxGNN knowledge graph has linked “Glucagon” to IBS via this shared lineage/naming proximity with GLP-1 pathways, rather than through direct evidence for glucagon hormone itself.
Given this, the mechanistic plausibility of Glucagon (as distinct from GLP-1 receptor agonists) being effective in IBS should be treated with caution pending clarification of drug identity and a dedicated mechanism-of-action review.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01056107 | Phase 1/2 | Completed | 52 | GLP-1 analogue ROSE-010 studied for effects on gastric emptying and gastric accommodation in constipation-predominant IBS (IBS-C) |
| NCT02731664 | Phase 1 | Completed | 12 | Native GLP-1 vs analogue ROSE-010 shown to inhibit prandial motility of stomach, duodenum and jejunum in humans |
| NCT04763564 | Phase 2 | Terminated | 8 | Liraglutide (GLP-1 analogue) vs placebo for chronic high bowel frequency after ileal pouch-anal anastomosis |
| NCT06408610 | N/A | Completed | 66 | Exercise intensity effects on gut dysbiosis and GLP-1 hormone levels in IBS patients |
| NCT05249023 | N/A | Completed | 37 | Mode of action of butyrate in the human colon, relevant to IBS and colon health |
| NCT03256266 | N/A | Active, not recruiting | 375 | Small intestinal organoid model to test effects of nutrient antigens/therapeutic agents |
| NCT04111263 | N/A | Completed | 33 | Gut-microbiota-targeted nutritional intervention for GI barrier integrity |
| NCT06333717 | N/A | Completed | 33 | Whole grain rye bread effects on gut-microbiota-brain axis and gut peptide release |
| NCT00802971 | N/A | Completed | 12 | Prevalence of idiopathic reactive hypoglycaemia and fructo-oligosaccharide effect on glucose variability |
| NCT06113146 | N/A | Completed | 41 | Effect of eating rate of ultra-processed foods on dietary intake and metabolic response |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40134805 | 2025 | Systematic review & meta-analysis | Frontiers in Endocrinology | GLP-1 receptor agonists (including ROSE-010) improve IBS symptoms by inhibiting the migrating motor complex and reducing GI motility |
| 35234561 | 2022 | Clinical study | Scandinavian Journal of Gastroenterology | ROSE-010 reduces pain during IBS attacks; cross-analysis identifies subpopulations most likely to respond |
| 28215540 | 2017 | Clinical study | Clinics and Research in Hepatology and Gastroenterology | Decreased serum GLP-1 correlates with abdominal pain in constipation-predominant IBS |
| 30444291 | 2019 | Review | Experimental Physiology | Reviews the role of L-cell-derived GLP-1 in IBS pathophysiology |
| 40697433 | 2025 | Observational | Annals of Gastroenterology | Real-world prescription and discontinuation patterns of GLP-1 receptor agonists in IBS patients |
| 40880735 | 2025 | Clinical study | Frontiers in Nutrition | Low FODMAP diet increases circulating GLP-1 in IBS patients |
| 31602785 | 2020 | Preclinical | Neurogastroenterology and Motility | GLP-1 agonist exendin-4 ameliorates GI dysfunction in a rat model of IBS |
| 31311066 | 2019 | Preclinical | Neurogastroenterology and Motility | Ghrelin sensitises rat colonic neurons to GLP-1 agonist exendin-4, relevant to postprandial IBS symptoms |
| 26765585 | 2016 | Review | Expert Opinion on Investigational Drugs | Review of novel investigational drugs, including GLP-1-related agents, for constipation-predominant IBS |
| 21694813 | 2011 | Review | Therapeutic Advances in Gastroenterology | Review of IBS treatments beyond fibre and antispasmodics, including emerging receptor-targeted agents |
UK Market Information
Glucagon holds no marketing authorisation recorded in this evidence pack for the UK (total licences: 0; market status: Not marketed). No product, dosage form, or approved indication data is therefore available.
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
(Note: TFDA/SmPC warnings and contraindications data are flagged as a Blocking data gap in this evidence pack (DG001) — an initial safety (S1) assessment cannot be completed until this is resolved.)
Conclusion and Next Steps
Decision: Hold
Rationale:
- The evidence base predominantly concerns GLP-1 receptor agonists, a related but mechanistically distinct peptide class, rather than glucagon itself — this identity ambiguity must be resolved before the prediction can be relied upon.
- Glucagon has no current UK marketing authorisation and no safety (SmPC) data is available, which blocks the standard S1 safety screening step.
To proceed, the following is needed:
- Confirm whether the TxGNN signal reflects glucagon hormone specifically or is an artefact of its shared proglucagon lineage with GLP-1 receptor agonists
- Obtain glucagon’s mechanism of action (MOA) data (DrugBank or equivalent)
- Obtain SmPC/product warnings and contraindications data (DG001, Blocking)
- If glucagon-specific evidence is confirmed to be minimal, consider whether this candidate should instead be reframed around the GLP-1 receptor agonist class
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.